INDICATIONS

Ketoconazole Cream 2% is indicated for the topical treatment
of tinea corporis, tinea cruris and tinea pedis caused by Trichophyton
rubrum, T. mentagrophytes and Epidermophyton floccosum; in the
treatment of tinea (pityriasis) versicolor caused by Malassezia furfur (Pityrosporum
orbiculare); in the treatment of cutaneouscandidiasis caused by Candida
spp. and in the treatment of seborrheic dermatitis.

DOSAGE AND ADMINISTRATION

Cutaneous candidiasis, tinea corporis, tinea cruris,
tinea pedis and tinea (pityriasis) versicolor: It is recommended that
Ketoconazole Cream 2% be applied once daily to cover the affected and immediate
surrounding area. Clinical improvement may be seen fairly soon after treatment
is begun; however, candidal infections and tinea cruris and corporis should be
treated for two weeks in order to reduce the possibility of recurrence.
Patients with tinea versicolor usually require two weeks of treatment. Patients
with tinea pedis require six weeks of treatment. Seborrheic dermatitis:
Ketoconazole Cream 2% should be applied to the affected area twice daily for
four weeks or until clinical clearing.

If a patient shows no clinical improvement after the
treatment period, the diagnosis should be redetermined.

SIDE EFFECTS

During clinical trials 45 (5.0%) of 905 patients treated
with Ketoconazole Cream 2% and 5 (2.4%) of 208 patients treated with placebo
reported side effects consisting mainly of severe irritation, pruritus and
stinging. One of the patients treated with Ketoconazole Cream developed a
painful allergic reaction.

In worldwide postmarketing experience, rare reports of
contact dermatitis have been associated with Ketoconazole Cream or one of its
excipients, namely sodium sulfite or propylene glycol.

DRUG INTERACTIONS

No information provided.

Warnings & Precautions

WARNINGS

Ketoconazole Cream 2% contains sodium sulfite anhydrous, a
sulfite that may cause allergic-type reactions including anaphylactic symptoms
and life-threatening or less severe asthmatic episodes in certain susceptible
people. The overall prevalence of sulfite sensitivity in the general population
is unknown and probably low. Sulfite sensitivity is seen more frequently in
asthmatic than in nonasthmatic people.

PRECAUTIONS

General

If a reaction suggesting sensitivity or chemical irritation
should occur, use of the medication should be discontinued. Hepatitis (1:10,000
reported incidence) and, at high doses, lowered testosterone and ACTH induced
corticosteroid serum levels have been seen with orally administered ketoconazole;
these effects have not been seen with topical ketoconazole.

Carcinogenesis, Mutagenesis, Impairment Of Fertility

A long-term feeding study in Swiss Albino mice and in Wistar
rats showed no evidence of oncogenic activity. The dominantlethal mutation
test in male and female mice revealed that single oral doses of ketoconazole as
high as 80 mg/kg produced no mutation in any stage of germ cell development.
The Ames'Salmonella microsomal activator assay was also negative.

Pregnancy

Teratogenic effects : Pregnancy Category C

Ketoconazole has been shown to be teratogenic (syndactylia
and oligodactylia) in the rat when given orally in the diet at 80 mg/kg/day,
(10 times the maximum recommended human oral dose). However, these effects may
be related to maternal toxicity, which was seen at this and higher dose levels.

There are no adequate and well-controlled studies in
pregnant women. Ketoconazole should be used during pregnancy only if the
potential benefit justifies the potential risk to the fetus.

Nursing Mothers

It is not known whether Ketoconazole Cream 2% administered
topically could result in sufficient systemic absorption to produce detectable
quantities in breast milk. Nevertheless, a decision should be made whether to
discontinue nursing or discontinue the drug, taking into account the importance
of the drug to the mother.

Pediatric Use

Safety and effectiveness in children have not been established.

Overdosage & Contraindications

OVERDOSE

No information provided.

CONTRAINDICATIONS

Ketoconazole Cream 2% is contraindicated in persons who have
shown hypersensitivity to the active or excipient ingredients of this
formulation.

Clinical Pharmacology

CLINICAL PHARMACOLOGY

When Ketoconazole Cream 2% was applied dermally to intact or
abraded skin of Beagle dogs for 28 consecutive days at a dose of 80 mg, there
were no detectable plasma levels using an assay method having a lower detection
limit of 2 ng/ml.

After a single topical application to the chest, back and
arms of normal volunteers, systemic absorption of ketoconazole was not detected
at the 5 ng/ml level in blood over a 72-hour period.

Two dermal irritancy studies, a human sensitization test, a
phototoxicity study and a photoallergy study conducted in 38 male and 62 female
volunteers showed no contact sensitization of the delayed hypersensitivity
type, no irritation, no phototoxicity and no photoallergenic potential due to Ketoconazole
Cream 2%.

Microbiology

Ketoconazole is a broad spectrum synthetic antifungal agent
which inhibits the in vitro growth of the following common dermatophytes and
yeasts by altering the permeability of the cell membrane: dermatophytes: Trichophyton
rubrum, T. mentagrophytes, T. tonsurans, Microsporum canis, M.

audouini, M. gypseum and Epidermophyton floccosum;
yeasts: Candida albicans, Malassezia ovale (Pityrosporum ovale)
and C. tropicalis; and the organism responsible for tinea versicolor,
Malassezia furfur (Pityrosporum orbiculare). Only those organisms listed in the
INDICATIONS AND USAGE Section have been proven to be clinically affected.
Development of resistance to ketoconazole has not been reported.

Mode Of Action

In vitro studies suggest that ketoconazole impairs the
synthesis of ergosterol, which is a vital component of fungal cell membranes.
It is postulated that the therapeutic effect of ketoconazole in seborrheic
dermatitis is due to the reduction of M. ovale, but this has not yet been
proven.